The bare lymphocyte syndrome, type II (BLS II) is a rare recessive genetic condition in which a group of genes called major histocompatibility complex class II (MHC class II) are not expressed.

The result is that the immune system is severely compromised and cannot effectively fight infection. Clinically, this is similar to severe combined immunodeficiency (SCID), in which lymphocyte precursor cells are improperly formed. As a notable contrast, however, bare lymphocyte syndrome does not result in decreased B- and T-cell counts, as the development of these cells is not impaired.

Diarrhea can be among the associated conditions.

Bare lymphocyte syndrome is a condition caused by mutations in certain genes of the major histocompatibility complex or involved with the processing and presentation of MHC molecules. It is a form of severe combined immunodeficiency.

Clinical appearance is variable with presentation ranging from gray to yellowish brown, but the characteristic features is the translucent or opalescent hue to the teeth.

In Type I, primary teeth are more severely affected compared to the permanent dentition which has more varied features, commonly involving lower incisors & canines. Primary teeth have a more obvious appearance as it has a thinner layer of enamel overlying dentine, hence the color of dentine is more noticeable.

In Type II, both the dentitions are equally affected.

Enamel is usually lost early because it is further inclined to attrition due to loss of scalloping at the dentoenamel junction (DEJ). It was suggested that the scalloping is beneficial for the mechanical properties of teeth as it reinforces the anchor between enamel and dentine. However, the teeth are not more susceptible to dental caries than normal ones.

However, certain patients with dentinogenesis imperfecta will suffer from multiple periapical abscesses apparently resulting from pulpal strangulation secondary to pulpal obliteration or from pulp exposure due to extensive coronal wear. They may need apical surgery to save the involved teeth.

These features are also present in dentine dysplasia and hence, the condition may initially be misdiagnosed.

Type I: DI associated with Osteogenesis Imperfecta (OI). Type of DI with similar dental abnormalities usually an autosomal dominant trait with variable expressivity but can be recessive if the associated osteogenesis imperfecta is of recessive type.

Type II: DI not associated with OI. Occurs in people without other inherited disorders (i.e. Osteogenesis imperfecta). It is an autosomal dominant trait. A few families with type II have progressive hearing loss in addition to dental abnormalities. Also called hereditary opalescent dentin.

Type III: Brandywine isolate. This type is rare with occurrences only in the secluded populations at Maryland, USA. its predominant characteristic is bell-shaped crowns, especially in the permanent dentition. Unlike Types I and II, it involves teeth with shell-like appearance and multiple pulp exposures.

Mutations in the "DSPP" gene have been identified in people with type II and type III dentinogenesis imperfecta. Type I occurs as part of osteogenesis imperfecta.

The specific problems produced differ according to the particular abnormal synthesis involved. Common manifestations include ataxia; seizures; retinopathy; liver fibrosis; coagulopathies; failure to thrive; dysmorphic features ("e.g.," inverted nipples and subcutaneous fat pads; and strabismus. If an MRI is obtained, cerebellar atrophy and hypoplasia is a common finding.

Ocular abnormalities of CDG-Ia include: myopia, infantile esotropia, delayed visual maturation, low vision, optic disc pallor, and reduced rod function on electroretinography.

Three subtypes of CDG I (a,b,d) can cause congenital hyperinsulinism with hyperinsulinemic hypoglycemia in infancy.

Thiel–Behnke dystrophy, or Corneal dystrophy of Bowman layer, type II, is a rare form of corneal dystrophy affecting the layer that supports corneal epithelium.

The dystrophy was first described in 1967 and initially suspected to denote the same entity as the earlier-described Reis-Bucklers dystrophy, but following a study in 1995 by Kuchle et al. the two look-alike dystrophies were deemed separate disorders.

Collagen improperly formed, enough collagen is made but it is defective.

- Bones fracture easily, sometimes even before birth

- Bone deformity, often severe

- Respiratory problems possible

- Short stature, spinal curvature and sometimes barrel-shaped rib cage

- Triangular face

- Loose joints (double-jointed)

- Poor muscle tone in arms and legs

- Discolouration of the sclera (the 'whites' of the eyes are blue)

- Early loss of hearing possible

Type III is distinguished among the other classifications as being the "progressive deforming" type, wherein a neonate presents with mild symptoms at birth and develops the aforementioned symptoms throughout life. Lifespans may be normal, albeit with severe physical handicapping.

Nodular sclerosis (or "NSHL") is a form of Hodgkin's lymphoma that is the most common subtype of HL in developed countries. It affects females slightly more than males and has a median age of onset at ~28 years. It is composed of large tumor nodules with lacunar Reed–Sternberg cell (RS cells) surrounded by fibrotic collagen bands.

The British National Lymphoma Investigation further categorized NSHL based upon Reed-Sternberg cells into "nodular sclerosis type I" (NS I) and "nodular sclerosis type II" (NS II), with the first subtype responding better to treatment.

Mucolipidosis II (ML II) is a particularly severe form of ML that has a significant resemblance to another mucopolysaccharidoses called Hurler syndrome. Generally only laboratory testing can distinguish the two as the presentation is so similar. There are high plasma levels of lysosomal enzymes and are often fatal in childhood. Typically, by the age of 6 months, failure to thrive and developmental delays are obvious symptoms of this disorder. Some physical signs, such as abnormal skeletal development, coarse facial features, and restricted joint movement, may be present at birth. Children with ML II usually have enlargement of certain organs, such as the liver (hepatomegaly) or spleen (splenomegaly), and sometimes even the heart valves. Affected children often have stiff claw-shaped hands and fail to grow and develop in the first months of life. Delays in the development of their motor skills are usually more pronounced than delays in their cognitive (mental processing) skills. Children with ML II eventually develop a clouding on the cornea of their eyes and, because of their lack of growth, develop short-trunk dwarfism (underdeveloped trunk). These young patients are often plagued by recurrent respiratory tract infections, including pneumonia, otitis media (middle ear infections), bronchitis and carpal tunnel syndrome. Children with ML II generally die before their seventh year of life, often as a result of congestive heart failure or recurrent respiratory tract infections.

Symptoms of ML I are either present at birth or develop within the first year of life. In many infants with ML I, excessive swelling throughout the body is noted at birth. These infants are often born with coarse facial features, such as a flat nasal bridge, puffy eyelids, enlargement of the gums, and excessive tongue size (macroglossia). Many infants with ML I are also born with skeletal malformations such as hip dislocation. Infants often develop sudden involuntary muscle contractions (called myoclonus) and have red spots in their eyes (cherry red spots). They are often unable to coordinate voluntary movement (called ataxia). Tremors, impaired vision, and seizures also occur in children with ML I. Tests reveal abnormal enlargement of the liver (hepatomegaly) and spleen (splenomegaly) and extreme abdominal swelling. Infants with ML I generally lack muscle tone (hypotonia) and have mental retardation that is either initially or progressively severe. Many patients suffer from failure to thrive and from recurrent respiratory infections. Most infants with ML I die before the age of 1 year.

Collagen quantity is sufficient but is not of a high enough quality

- Bones fracture easily, especially before puberty

- Short stature, spinal curvature, and barrel-shaped rib cage

- Bone deformity is mild to moderate

- Early loss of hearing

Similar to Type I, Type IV can be further subclassified into types IVA and IVB characterized by absence (IVA) or presence (IVB) of dentinogenesis imperfecta.

Mutations in several genes have been associated with the traditional clinical syndromes, termed muscular dystrophy-dystroglycanopathies (MDDG). A new nomenclature based on clinical severity and genetic cause was recently proposed by OMIM. The severity classifications are A (severe), B (intermediate), and C (mild). The subtypes are numbered one to six according to the genetic cause, in the following order: (1) POMT1, (2) POMT2, (3) POMGNT1, (4) FKTN, (5) FKRP, and (6) LARGE.

Most common severe types include:

Many affected individuals have yellowing of the skin and eyes (jaundice) and an enlarged liver and spleen (hepatosplenomegaly). This condition also causes the body to absorb too much iron, which builds up and can damage tissues and organs. In particular, iron overload can lead to an abnormal heart rhythm (arrhythmia), congestive heart failure, diabetes, and chronic liver disease (cirrhosis). Rarely, people with CDA type I are born with skeletal abnormalities, most often involving the fingers and/or toes.

Congenital dyserythropoietic anemia type I (CDA I) is a disorder of blood cell production, particularly of

the production of erythroblasts, which are the precursors of the red blood cells (RBCs).

The mucopolysaccharidoses share many clinical features but have varying degrees of severity. These features may not be apparent at birth but progress as storage of glycosaminoglycans affects bone, skeletal structure, connective tissues, and organs. Neurological complications may include damage to neurons (which send and receive signals throughout the body) as well as pain and impaired motor function. This results from compression of nerves or nerve roots in the spinal cord or in the peripheral nervous system, the part of the nervous system that connects the brain and spinal cord to sensory organs such as the eyes and to other organs, muscles, and tissues throughout the body.

Depending on the mucopolysaccharidosis subtype, affected individuals may have normal intellect or have cognitive impairments, may experience developmental delay, or may have severe behavioral problems. Many individuals have hearing loss, either conductive (in which pressure behind the eardrum causes fluid from the lining of the middle ear to build up and eventually congeal), neurosensory (in which tiny hair cells in the inner ear are damaged), or both. Communicating hydrocephalus—in which the normal reabsorption of cerebrospinal fluid is blocked and causes increased pressure inside the head—is common in some of the mucopolysaccharidoses. Surgically inserting a shunt into the brain can drain fluid. The eye's cornea often becomes cloudy from intracellular storage, and glaucoma and degeneration of the retina also may affect the patient's vision.

Physical symptoms generally include coarse or rough facial features (including a flat nasal bridge, thick lips, and enlarged mouth and tongue), short stature with disproportionately short trunk (dwarfism), dysplasia (abnormal bone size and/or shape) and other skeletal irregularities, thickened skin, enlarged organs such as liver (hepatomegaly) or spleen (splenomegaly), hernias, and excessive body hair growth. Short and often claw-like hands, progressive joint stiffness, and carpal tunnel syndrome can restrict hand mobility and function. Recurring respiratory infections are common, as are obstructive airway disease and obstructive sleep apnea. Many affected individuals also have heart disease, often involving enlarged or diseased heart valves.

Another lysosomal storage disease often confused with the mucopolysaccharidoses is mucolipidosis. In this disorder, excessive amounts of fatty materials known as lipids (another principal component of living cells) are stored, in addition to sugars. Persons with mucolipidosis may share some of the clinical features associated with the mucopolysaccharidoses (certain facial features, bony structure abnormalities, and damage to the brain), and increased amounts of the enzymes needed to break down the lipids are found in the blood.

Affected feet may become numb, by erythema (turning red) or cyanosis (turning blue) as a result of poor blood supply, and may begin emanating a decaying odor if the early stages of necrosis (tissue death) set in. As the condition worsens, feet may also begin to swell. Advanced trench foot often involves blisters and open sores, which lead to fungal infections; this is sometimes called tropical ulcer (jungle rot). If left untreated, trench foot usually results in gangrene, which may require amputation. If trench foot is treated properly, complete recovery is normal, though it is marked by severe short-term pain when feeling returns.

The condition is marked by progressive deterioration, hepatosplenomegaly, dwarfism, and unique facial features. A progressive mental retardation occurs, with death frequently occurring by the age of 10 years.

Developmental delay is evident by the end of the first year, and patients usually stop developing between ages 2 and 4. This is followed by progressive mental decline and loss of physical skills. Language may be limited due to hearing loss and an enlarged tongue. In time, the clear layers of the cornea become clouded and retinas may begin to degenerate. Carpal tunnel syndrome (or similar compression of nerves elsewhere in the body) and restricted joint movement are common.

Affected children may be large at birth and appear normal, but may have inguinal (in the groin) or umbilical (where the umbilical cord passes through the abdomen) hernias. Growth in height may be initially faster than normal, then begins to slow before the end of the first year and often ends around age 3. Many children develop a short body trunk and a maximum stature less than 4 feet. Distinct facial features (including flat face, depressed nasal bridge, and bulging forehead) become more evident in the second year. By age 2, the ribs have widened and are oar-shaped. The liver, spleen, and heart are often enlarged. Children may experience noisy breathing and recurring upper respiratory-tract and ear infections. Feeding may be difficult for some children, and many experience periodic bowel problems. Children with Hurler syndrome often die before age 10 from obstructive airway disease, respiratory infections, or cardiac complications.

To clarify whether Thiel–Behnke corneal dystrophy is a separate entity from Reis-Bucklers corneal dystrophy, Kuchle et al. (1995) examined 28 corneal specimens with a clinically suspected diagnosis of corneal dystrophy of the Bowman layer by light and electron microscopy and reviewed the literature and concluded that 2 distinct autosomal dominant corneal dystrophy of Bowman layer (CBD) exist and proposed the designation CDB type I (geographic or 'true' Reis-Bucklers dystrophy) and CDB type II (honeycomb-shaped or Thiel–Behnke dystrophy). Visual loss is significantly greater in CDB I, and recurrences after corneal transplantation seem to be earlier and more extensive in CDB I.

The role of sialidase is to remove a particular form of sialic acid (a sugar molecule) from sugar-protein complexes (referred to as glycoproteins), which allows the cell to function properly. Because the enzyme is deficient, small chains containing the sugar-like material accumulate in neurons, bone marrow, and various cells that defend the body against infection.

At the beginning, affected individuals often notice the loss of pain and temperature sensation or all sensory modalities in their feet. As the disease progresses, the sensory abnormalities may extend up to the knees. However, they often do not notice sensory loss for a long time. Many affected individuals only become aware of the disease when they notice painless injuries and burns or when they seek medical advice for slowly healing wounds or foot ulcers. Foot ulcerations may appear due to permanent pressure, such as long walks or badly fitting shoes. Minor wounds or blisters may then lead to deep foot ulcerations. Once infection occurs, complications such as inflammation and destruction of the underlying bones may follow. Affected individuals who do not lose sensation may experience spontaneous pain. In addition, many affected individuals exhibit, to a variable degree, symmetrical distal muscle weakness and wasting.

HSAN I is characterized by marked sensory disturbances mainly as the loss of pain and temperature sensation in the distal parts of the lower limbs. The loss of sensation can also extend to the proximal parts of the lower limbs and the upper limbs as the disease progresses. Some affected individuals do not lose sensation, but instead experience severe shooting, burning, and lancinating pains in the limbs or in the trunk. Autonomic disturbances, if present, manifest as decreased sweating. The degree of motor disturbances is highly variable, even within families, ranging from absent to severe distal muscle weakness and wasting.

The disease progresses slowly, but often disables the affected individuals severely after a long duration. The onset of the disease varies between the 2nd and 5th decade of life, albeit congenital or childhood onset has occasionally been reported. With the progression of the disease, the affected individuals lose the ability to feel pain in their feet and legs. Minor injuries in the painless area can result in slow-healing wounds which, if not immediately recognized, can develop into chronic ulcerations. Once infection occurs, these ulcerations can result in severe complications that lead to foot deformity, such as inflammation of the underlying bones, spontaneous bone fractures, and progressive degeneration of weight-bearing joints. Furthermore, foot deformity promotes skin changes such as hyperkeratosis at pressure points. These complications may necessitate amputation of the affected foot.

Biopsies of severely affected sural nerve (short saphenous nerve) in patients with HSAN I showed evidence of neuronal degeneration. Only a very few myelinated fibers were observed some of which showed a sign of primary (segmental) demyelination. A reasonable number of unmyelinated axons remained, although the presence of stacks of flattened Schwann cell processes suggested unmyelinated axon loss. Electrophysiological testing provides additional evidence that neuronal degeneration underlies the disease. Sensory potentials are usually absent in the lower limbs but are often recordable or even normal in the upper limbs of the patients. In addition, motor conduction is slow, possibly implying a demyelinating process.

MPS VII, Sly syndrome, one of the least common forms of the mucopolysaccharidoses, is estimated to occur in fewer than one in 250,000 births. The disorder is caused by deficiency of the enzyme beta-glucuronidase. In its rarest form, Sly syndrome causes children to be born with hydrops fetalis, in which extreme amounts of fluid are retained in the body. Survival is usually a few months or less. Most children with Sly syndrome are less severely affected. Neurological symptoms may include mild to moderate intellectual disability by age 3, communicating hydrocephalus, nerve entrapment, corneal clouding, and some loss of peripheral and night vision. Other symptoms include short stature, some skeletal irregularities, joint stiffness and restricted movement, and umbilical and/or inguinal hernias. Some patients may have repeated bouts of pneumonia during their first years of life. Most children with Sly syndrome live into the teenage or young adult years.

The three most common symptoms of Opitz G/BBB syndrome (both type I & II) are hypertelorism (exceptionally wide-spaced eyes), laryngo-tracheo-esophalgeal defects (including clefts and holes in the palate, larynx, trachea and esophagus) and hypospadias (urinary openings in males not at the tip of the penis) (Meroni, Opitz G/BBB syndrome, 2012). Abnormalities in the larynx, trachea and esophagus can cause significant difficulty breathing and/or swallowing and can result in reoccurring pneumonia and life-threatening situations. Commonly, there may be a gap between the trachea and esophagus, referred to as a laryngeal cleft; which can allow food or fluid to enter the airway and make breathing and eating a difficult task.

Genital abnormalities like a urinary opening under the penis (hypospadias), undescended testes (cryptorchidism), underdeveloped scrotum and a scrotum divided into two lobes (bifid scrotum) can all be commonplace for males with the disease.

Developmental delays of the brain and nervous system are also common in both types I and II of the disease. 50% of people with Opitz G/BBB Syndrome will experience developmental delay and mild intellectual disability. This can impact motor skills, speech and learning capabilities. Some of these instances are likened to autistic spectrum disorders. Close to half of the people with Opitz G/BBB Syndrome also have a cleft lip (hole in the lip opening) and possibly a cleft palate (hole in the roof of the mouth), as well. Less than half of the people diagnosed have heart defects, imperforate anus (obstructed anal opening), and brain defects. Of all the impairments, female carriers of X-linked Type I Opitz G/BBB Syndrome usually only have ocular hypertelorism.

Hurler syndrome, also known as mucopolysaccharidosis type I (MPS I), Hurler's disease, also gargoylism, is a genetic disorder that results in the buildup of glycosaminoglycans (formerly known as mucopolysaccharides) due to a deficiency of alpha-L iduronidase, an enzyme responsible for the degradation of mucopolysaccharides in lysosomes. Without this enzyme, a buildup of heparan sulfate and dermatan sulfate occurs in the body. Symptoms appear during childhood and early death can occur due to organ damage.

MPS I is divided into three subtypes based on severity of symptoms. All three types result from an absence of, or insufficient levels of, the enzyme α-L-iduronidase. MPS I H or Hurler syndrome is the most severe of the MPS I subtypes. The other two types are MPS I S or Scheie syndrome and MPS I H-S or Hurler-Scheie syndrome.

Hurler syndrome is often classified as a lysosomal storage disease, and is clinically related to Hunter syndrome, which is X-linked, while Hurler syndrome is autosomal recessive.

It is named for Gertrud Hurler (1889–1965), a German pediatrician.

Different people are affected very differently by this disease. The main manifestation is fluid-filled cysts that grow on the brain and can cause damage that varies depending on their location and severity. Symptoms may manifest early in infancy, or may manifest as late as adulthood. Symptoms associated with autosomal dominant porencephaly type I include migraines, hemiplegia or hemiparesis, seizures, cognitive impairment, strokes, dystonia, speech disorders, involuntary muscle spasms, visual field defects, and hydrocephalus.

X-linked type I Opitz G/BBB Syndrome is diagnosed on clinical findings, but those findings can vary greatly: even within the same family. Manifestations of X-linked type I are classified in the frequent/major findings and minor findings that are found in less than 50% of individuals.

The three major findings that suggest a person has X-linked Type I Opitz G/BBB Syndrome:

1. Ocular hypertelorism (~100% cases)

2. Hypospadias (85-90% cases)

3. Laryngotracheoesophageal abnormalities (60-70%)

Minor findings found in less than 50% of individuals:

1. Developmental delay (especially intellectually)

2. Cleft lip/palate

3. Congenital heart defects

4. Imperforate (blocked) anus

5. Brain defects (especially corpus callosum)

In 1989, Hogdall used ultrasonographs to diagnose X-linked Type I Opitz G/BBB Syndrome after 19 weeks of pregnancy, by identifying hypertelorism (widely-spaced eyes) and hypospadias (irregular urinary tract openings in the penis).

There is also molecular genetic testing available to identify mutations leading to Opitz G/BBB Syndrome. X-linked Type I testing must be done on MID1, since this is the only gene that is known to cause Type I Opitz G/BBB Syndrome. Two different tests can be performed: sequence analysis and deletion/duplication analysis. In the sequence analysis a positive result would detect 15-50% of the DNA sequence mutated, while a deletion/duplication positive result would find deletion or duplication of one or more exons of the entire MID1 gene.